Many different agents are known to possess biological activity, including therapeutic activity, and for many of these the molecular mechanism of action is known. Thus, such compounds may be determined to be related to each other in that they have a common mechanism of action, which mechanism may bear some relationship to the chemical properties of the compounds or to their overall molecular shape. Alternatively, such compounds may not be similar in overall molecular shape or properties but may still, for diverse reasons, operate biologically in a similar manner. In addition, such compounds, related by mechanism of action (MOA) may also show other properties in common and thus these MOA-related sets of compounds may be formed into distinct groups based on their common biological activity.
In a similar way, diverse cells may be related in terms of their susceptibility to a given chemical agent, or test compound, which may act by modifying the expression profile of a given set of genes within the genome of the cells. Thus, an expression profile may be formulated for a given gene set, the latter being some subset of the genome of the cell, and this expression profile may be modulated by the presence of a particular chemical agent. It would be advantageous to be able to take advantage of such a relationship based on common expression profiles, especially where the given gene set is related to a disease process or to the viability of the cell.
Because methods of analyzing gene expression are subject to use in large screening assays, where such methods, including rapid measurement of messenger RNA species coupled with methods of reverse transcriptase-polymerase chain reaction amplification for ease of measurement, are susceptible to high degrees of automation, such genetic methods present themselves as a ready medium for high throughput screening for agents having a selected biological activity.
Heretofore many expression profiles of diverse gene sets of different cells have been determined and most are available in public data bases. In addition, workers in the disease treatment area have attempted to determine expression profiles of cells in different diseases, such as cancer, in the hopes of finding an agent that changes the expression profile and thereby serves to alleviate the disease condition, such as by killing the cell involved (for example, a cancer cell). However, one problem with this approach is that one does not know beforehand whether a given disease is amenable to treatment with a given therapeutic agent and consequently large scale screening processes have been developed, with time and expense a major factor. Since many known therapeutic agents are already available it would be advantageous if one could ascertain the likelihood that a given cell would be susceptible to a given agent before embarking on large scale screening processes.
The present invention solves this problem by taking advantage of such methods to provide expression profiles of different cells. In so doing, the likely susceptibility of a cell to a selected therapeutic agent can be determined by finding cells with the same gene expression profile as a cell known to be susceptible to said therapeutic agent and where said agent modulates the expression profile of the given gene set.